1. Technical Field
This invention relates to methods for non-invasively determining biological tissue oxygenation in general, and to non-invasive methods utilizing near-infrared spectroscopy (NIRS) techniques in particular.
2. Background Information
Oxygen saturation in a mammalian subject can be defined as:
                                          O            2                    ⁢                                          ⁢          saturation          ⁢                                          ⁢          %                =                                            HbO              2                                      (                                                HbO                  2                                +                Hb                            )                                *          100          ⁢          %                                    (                  Eqn          .                                          ⁢          1                )            where HbO2 refers to oxygenated hemoglobin (i.e., “oxyhemoglobin”) and Hb refers to deoxygenated hemoglobin (i.e., “deoxyhemoglobin”). In the arterial circulatory system under normal conditions, there is a high proportion of HbO2 to Hb, resulting in an arterial oxygen saturation (defined as SaO2%) of 95-100%. After delivery of oxygen to tissue via the capillaries, the proportion of HbO2 to Hb decreases. Therefore, the measured oxygen saturation of venous blood (defined as SvO2%) is lower and may be about 70%.
One spectrophotometric method, called pulse oximetry, determines arterial oxygen saturation (SaO2) of peripheral tissue (i.e. finger, ear, nose) by monitoring pulsatile optical attenuation changes of detected light induced by pulsatile arterial blood volume changes in the arteriolar vascular system. The method of pulse oximetry requires pulsatile blood volume changes in order to make a measurement. Since venous blood is not pulsatile, pulse oximetry cannot provide any information about venous blood.
Near-infrared spectroscopy (NIRS) is an optical spectrophotometric method of continually monitoring tissue oxygenation that does not require pulsatile blood volume to calculate parameters of clinical value. The NIRS method utilizes light in the near-infrared range (700 to 1,000 nm) that can pass easily through skin, bone and other tissues where it encounters hemoglobin located mainly within micro-circulation passages; e.g., capillaries, arterioles, and venuoles. Hemoglobin exposed to light in the near infra-red range has specific absorption spectra that varies depending on its oxidation state; i.e., oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) each act as a distinct chromophore. By using light sources that transmit near-infrared light at specific different wavelengths, and measuring changes in transmitted or reflected light attenuation, concentration changes of the oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) can be monitored.
The apparatus used in NIRS analysis typically includes a plurality of light sources, one or more light detectors for detecting reflected or transmitted light, and a processor for processing signals that represent the light emanating from the light source and the light detected by the light detector. Light sources such as light emitting diodes (LEDs) or laser diodes that produce light emissions in the wavelength range of 700-1000 nm at an intensity below that which would damage the biological tissue being examined are typically used. A photodiode or other light source detector is used to detect light reflected from or passed through the tissue being examined. The processor takes the signals from the light sources and the light detector and analyzes those signals in terms of their intensity and wave properties.
It is known that relative changes of the concentrations of HbO2 and Hb can be evaluated using apparatus similar to that described above, including a processor programmed to utilize a variant of the Beer-Lambert Law, which accounts for optical attenuation in a highly scattering medium like biological tissue. The modified Beer-Lambert Law can be expressed as:Aλ=−log(I/Io)λ=αλ*C*d*Bλ+G  (Eqn. 2)wherein “Aλ,” represents the optical attenuation in tissue at a particular wavelength λ (units: optical density or OD); “Io” represents the incident light intensity (units: W/cm2); “I” represents the detected light intensity; “αλ” represents the wavelength dependent absorption coefficient of the chromophore (units: OD*cm−1*μM−1); “C” represents the concentration of chromophore (units: μM); “d” represents the light source to detector (optode) separation distance (units: cm); “Bλ” represents the wavelength dependent light scattering differential pathlength factor (unitless); and “G” represents light attenuation due to scattering within tissue (units: OD). The product of “d*Bλ” represents the effective pathlength of photon traveling through the tissue.
Absolute measurement of chromophore concentration (C) is very difficult because G is unknown or difficult to ascertain. However, over a reasonable measuring period of several hours to days, G can be considered to remain constant, thereby allowing for the measurement of relative changes of chromophore from a zero reference baseline. Thus, if time t1 marks the start of an optical measurement (i.e., a base line) and time t2 is an arbitrary point in time after t1, a change in attenuation (ΔA) between t1 and t2 can be calculated, and variables G and Io will cancel out providing that they remain constant.
The change in chromophore concentration (ΔC=C(t2)−C(t1)) can be determined from the change in attenuation ΔA, for example using the following equation derived from the modified Beer-Lambert Law:ΔAλ=−log(It2/It1)λ=αλ*ΔC*d*Bλ  (Eqn. 3)Presently known NIRS algorithms that are designed to calculate the relative change in concentration of more than one chromophore use a multivariate form of Equation 2 or 3. To distinguish between, and to compute relative concentration changes in, oxyhemoglobin (ΔHbO2) and deoxyhemoglobin (ΔHb), a minimum of two different wavelengths are typically used. The concentration of the HbO2 and Hb within the examined tissue is determined in μmoles per liter of tissue (μM).
The above-described NIRS approach to determining oxygenation levels is useful, but it is limited in that it only provides information regarding a change in the level of oxygenation within the tissue. It does not provide a means for determining the absolute value of oxygen saturation within the biological tissue.
At present, information regarding the relative contributions of venous and arterial blood within tissue examined by NIRS is either arbitrarily chosen or is determined by invasive sampling of the blood as a process independent from the NIRS examination. For example, it has been estimated that NIRS examined brain tissue comprising about 60 to 80% blood venous and about 20 to 40% arterial blood. Blood samples from catheters placed in venous drainage sites such as the internal jugular vein, jugular bulb, or sagittal sinus have been used to evaluate NIRS measurements. Results from animal studies have shown that NIRS interrogated tissue consists of a mixed vascular bed with a venous-to-arterial ratio of about 2:1 as determined from multiple linear regression analysis of sagittal sinus oxygen saturation (SssO2) and arterial oxygen saturation (SaO2). An expression representing the mixed venous/arterial oxygen saturation (SmvO2) in NIRS examined tissue is shown by the equation:SmvO2=Kv*SvO2+Ka*SaO2  (Eqn. 4)where “SvO2” represents venous oxygen saturation; “SaO2” represents arterial oxygen saturation; and Kv and Ka are the weighted venous and arterial contributions respectively, with Kv+Ka=1. The parameters Kv and Ka may have constant values, or they may be a function of SvO2 and SaO2. Determined oxygen saturation from the internal jugular vein (SijvO2), jugular bulb (SjbO2), or sagittal sinus (SssO2) can be used to represent SvO2. Therefore, the value of each term in Equation 4 is empirically determined, typically by discretely sampling or continuously monitoring and subsequently evaluating patient arterial and venous blood from tissue that the NIRS sensor is examining, and using regression analysis to determine the relative contributions of venous and arterial blood independent of the NIRS examination.
Some medical procedures involve limiting or completely stopping the flow of blood to an organ. For example, some procedures involve isolating the heart from the rest of the body by means of a cross clamp on the aorta and then cold cardioplegia is given into the heart through the aortic root. The cold fluid (usually in the range of about 4-10° C.) ensures that the heart cools down to an approximate temperature of around 15-20° C. thus slowing down the metabolism of the heart and thereby preventing damage to the heart muscle. The process may be further augmented by a cardioplegic component which is high in potassium and magnesium. The potassium helps by arresting the heart in diastole thus ensuring that the heart does not use up the valuable energy stores during this period of heart isolation. Blood can be added to this solution especially for long procedures requiring more than half an hour of ascending aorta cross-clamp time. Blood acts as a buffer and also supplies nutrients to the heart during ischemia. Once the procedure on the heart vessels (e.g., coronary artery bypass grafting, or heart valve replacement, or correction of congenital heart defect, etc.) is over, the cross-clamp is removed and the isolation of the heart is terminated so that normal blood supply to the heart is restored and the heart starts beating again.
During the isolation period, it would be of great value to monitor the oxygen saturation level of the heart to ensure that the heart has a sufficient oxygen level to avoid damage.
The cessation of blood flow to an organ is not limited to hearts, however. For example, livers and kidneys are often removed from a donor for transplant into a recipient. In such cases, there would be value in knowing the oxygen saturation level in the organ before, during, and after the transplant.
What is needed, therefore, is a method for non-invasively determining the level of oxygen saturation within biological tissue that can determine the absolute oxygen saturation value rather than a change in level, and one that can be used to directly determine the oxygen saturation levels of a body organ.